Our research has as its general and overall goal the study of normal and aberrant intrathymic T-cell maturation. We have developed a number of monoclonal antibodies that define specific subsets of intrathymic T cells as well as subseta of thymic epithelial cells and thymic stromal cells within the human thymic microenvironment. We have used these monoclonal antibodies to characterize phenotypically and study the ontogeny of mesodermal-derived as well as endocrine epithelial components to the human thymic microenvironment. In addition, we have developed monoclonal antibodies that define the nonendocrine epithelial component of the thymus. We also have devised a system for in vitro long-term cultures of endocrine thymic epithelial cells, as well as in vitro culture of mesodermal-derived nonendocrine thymic stroma. Using a monoclonal antibody panel, we have identified a maturation pathway of human thymic epithelial cells both during ontogeny as well as throughout the postnatal life of the adult, and we have demonstrated phenotypic stages of thymic epithelial differentiation during this maturation pathway. Our future plane include investigating whether thymic epithelial maturation defined in vivo can be recapitulated in vitro. Moreover, we are studying the capacity of thymic epithelial cells at various stages of T-cell maturation in vitro to influence stages of T-cell differentiation. The long-term goal is to establish a reproducible in vitro assay system for promotion of various stages of human T-cell differentiation. (LB)